Regulatory agencies like the FDA, WHO, EU, and PIC/S have established validation guidelines and requirements for the pharmaceutical industry. Process validation is required to provide documented evidence that manufacturing processes produce consistent and quality products meeting specifications. It involves qualification of facilities, equipment, utilities, and processes. Validation studies include design qualification, installation qualification, operational qualification, and performance qualification. Regulatory guidelines cover validation of automated processes, suppliers' test results, sterilization processes, and analytical methods. A validation master plan and validation reports are required documentation.

1. REGULATORY REQUIREMENT
FOR VALIDATION IN
PHARMACEUTICAL INDUSTRY
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Presented by:
Vishal Ganda
M.Pharm ( 3rd Semester)
QAT-1ST Shift
Parul Institute of Pharmacy
Guided by:
Mrs. Nikita Patel
Asst. Professor
Parul Institute of Pharmacy

2. CONTENT
 DEFINATION AND IMPORTANCE
 HISTORY
 REGULATION UNDER US FDA
 REGULATION UNDER cGMP
 REGULATION UNDER WHO
 REGULATION UNDER EU
 REGULATION UNDER PIC/S
 VALIDATION MASTER PLAN
 VALIDATION REPORT
 CONCLUSION
 REFERENCE
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3. DEFINATION
 Validation - Process validation is the establishment of
documented evidence, which provide a high degree
of assurance that a specific process (manufacturing of
pharmaceutical dosage form) will consistently produce
a product meeting its predetermined specifications.
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4. IMPORTANCE OF VALIDATION
 Quality assurance cost reduction
 Customer satisfaction
 Product liability
 Fewer product recall
 Fewer batch failures
 Decreases risk of regulatory non compliance
 Smooth running of process
 Less in process control and end product testing
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5. HISTORICAL BACKGROUND FOR THE
REGULATORY BASIS
 The emphasis on validation began in the late 1970s, the requirement
has been set at 1963 as cGMP regulations for finished
pharmaceuticals.
 Validation is an integral part of QualityAssurance & its meaning is
“Action of providing an evidence”.
 Validation is necessarily include process qualification (qualification of
rawmaterials,equipment,system) under the section 21 CFR 211.100
which states:
“There shall be written procedures for production and
process control designed to assure that the drug products have the
identity, strength, quality, and purity”.
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6. HISTORY
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 The Kefauver-Harris Amendments to the FD&C Act were approved in1962
with Section 501(a)(2)(B) as an amendment.
 The result of The amendments Provided an additional powerful regulatory
tool to FDA to stop particular manufacturing process when the drug
product is deemed to adulteration.
 The Drug Product Quality Assurance Program of the 1960s and 1970s
involved first conducting a massive sampling and testing program of finished
batches.
 The investigation of clinical failures of several products(including Digoxin,
Digitoxin, Prednisolone, and Prednisone) by FDA found significant content
uniformity problems that were the result of poorly controlled manufacturing
processes

7. REGULATORY BASIS
 The regulatory basis validation program of process validation
is embodied within the regulations & guidelines provided by
cGMP & FDA.
 The ultimate legal authority is Sec501(a)(2)(B) by the FD&C
Act, which states “Drug is deemed to be adulterated due to
the methods/ facilities used for the manufacturing, processing,
packing/holding fails to administer in conformity – cGMP”
 Validation-Process validation is not just an FDA or U.S.
requirement. Similar requirements included in the World
Health Organization (WHO), the Pharmaceutical Inspection
Co-operation Scheme (PIC/S), and the European Union(EU).
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8. REGULATIONS FOR VALIDATION UNDER
USFDA
 Section211.100(a): Written procedures/deviations.
“There shall be written procedures for production and process control
designed to assure that the drug products have the identity, strength,
quality, and purity.”
 Section 211.110: Sampling and testing of in-process materials and drug
products
"....control procedures shall be established to monitor the output and
Validate the performance of those manufacturing processes that may
be responsible for causing variability in the characteristics of in-process
material and the drug product”
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9.  21CFR211.133: Control of Microbiological Contamination
" Appropriate written procedures, designed to prevent microbiological
contamination of drug products purporting to be sterile, shall be
established and followed. Such procedures shall include Validation of
any sterilization process.“
 FDA must inspect every drug manufacturing establishment at least once
every 2 years .
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19. REGULATORY REQUIREMENT FOR
VALIDATION IN cGMP
 The first cGMP regulations, based largely on the
Pharmaceutical Manufacturers Association’s-manufacturing
control guidelines .
 the Medicines Act (1968) covers most aspects of cGMP
in what is commonly referred to as "The Orange Guide"
 Validation under document of cGMP covers
procedure, process qualification, equipment,& facilities.
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20. 211.68 :validation of automated process.
211.84(d)(2): validation of supplier’s test results for
components.
211.84(d)(3): validation of supplier’s test results for
container and closures.
211.110(a) : validation of manufacturing process to ensure
content uniformity& integrity.
211.1113(b): validation of sterilization process.
211.165 : validation of analytical methods.
By June 2010, the same GLP/GMP Validation requirements will
apply to all manufacturers of dietary supplements.
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21. PLANS OF FDA GMP
 The FDA plans to oversee 591 national GMP inspections in
2014 and 2015, reduced from 967 performed last year.
 Consequently the agency plans to perform 30 percent more
foreign GMP inspections, increasing last year’s total of 604 to a
new grand total of 843 inspections.
 Companies will now be chosen for inspection using the
agency’s risk-based inspection model that equates inspection
periodicity to company quality practices and procedures. This
risk based model develop specifically for FDA GMP PLANS use,
takes into account risk factors; such as, Class I recalls, adverse
events, as well as compliance history as it assigns an
appropriate inspection cycle.
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22. VALIDATION REQUIREMENT UNDER
WHO
 WHO (World Health Organization) cGMP Guidelines
state Validation studies are an essential part of current
good manufacturing practice (cGMP) and should be
conducted in accordance with predefined protocols.
 WHO validation definition:
The documented act of proving any procedure,
process, equipment, material, activity or system which
actually leads to the expected results.
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23.  DQ: Design Qualification IQ: Installation Qualification
 OQ : Operational qualifi. PQ: Performance qualification
 DQ: The compliance of the basic design (location plan) with
the user requirements & regulatory requirements should be
submitted & documented.
 IQ: Documentary evidence to prove that the premises &
equipment have been built & installed in compliance with
their specifications. IQ include:
1.Preventive maintenance.
2 .Equipment info.
3. Calibration.
4.Verification of the equipment.
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24.  OQ: A series of tests to measure the performance
capability of equipment. The OQ for HPLC system is the
operation of pump, injector & detector will be tested at
this stage.
 PQ: Process to verify that the system is repeatable &
capable for consistently producing a quality product.
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25. VALIDATION REQUIREMENT UNDER EU
 The European Union requirements for validation is an
extract from ICH Q8, Q9 and Q10 documented
guidelines and helps to study continuous process
verification
 EU Validation Definition:
Documented evidence that the process, operated
within established parameters, can perform effectively
and reproducibly,To produce a medicinal product
meeting its predetermined specifications and quality
attributes
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26.  Strategies of validation under EU includes:
1) Traditional process verification
2) Contineous process validation.(CPV)
3) Critical process parameter.(CPP)
4) Critical quality attributes.(CQA)
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27.  1) Traditional process verification : process validation should focus
on the control strategy, which primarily includes critical process
parameters and other relevant studies demonstrating that the
process is capable of delivering the desired product quality.
 2) Contineous process validation.(CPV): an alternative approach
to process validation in which manufacturing process performance
is continuously monitored & evaluated.
 3) Critical process parameter.(CPP):a process parameter whose
variability has an impact on a critical quality attribute and
therefore should be controlled to ensure the process produce the
desired quality.
 4) Critical quality attributes.(CQA):a physical ,chemical,biological
or microbiological property should be within an appropriate
limit,range to ensure product quality.
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28. VALIDATION REQUIREMENT UNDER
PIC/S
 According the EU Guidelines to Good Manufacturing
Practice for Medicinal Products in Annex 15 the principles of
qualification & validation of the PIC/S is given under
document PIC/S PI 006-3:
 Doc states:
GMP for medicinal products Recommendations on
Validation Master Plan Installation and Operational
Qualification( Non-Sterile Process Validation Cleaning
Validation) can assist with the interpretation and the
implementation.
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29.  This document applies primarily to inspectorates of the
PIC/S member for whom it is intended as instruction for
preparing an inspection, and as an advanced training
aid for qualification/validation
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30. PREREQUISITES FOR SUCCESSFULL
VALIDATION
 Experience
 Planning
 Resource
 Understanding & communication
 Training
 Sop’s instrument & methodologies.
 Validation master plan
 Data analysis
 Validation report
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31. VALIDATION MASTER PLAN
 The complete overview of validation operation, organization
structure, content &planning in the form of a document is the
VMP.
 VMP shoud contain following data:
1) Validation policy of company,location & schedule
2) List of product,processes & system to be validated.
3) Installation & qualification for new equipment.
4) Key acceptance criteria.
5) Documentation formet used for protocols &report.
6) Time planning & scheduling of project.
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32.  The Validation Master Plan is a top layer document and
should not go into specific detail; but present an overall
picture of the company facility, organisation and
capability.
 It must give a clear and concise overview, to a
reviewer, of how the company has integrated all the
applicable cGMP requirements into every aspect of its
operations.
 It must define validation activities and allot
responsibilities for authoring, reviewing, approving, and
executing validation documentation and tasks.
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33. VALIDATION REPORT
 The validation report should be approved prior to product
distribution and kept permanently on file in quality assurance.
 The validation report should have a conclusion that explains
the manufacturing specialist’s (preparer’s) statement and
opinion.
 The validation report should contain the approved validation
protocol, tabulated or graphical results, process monitoring
(forms), and all analytical results of the validation batches.
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34. CONCLUSION
 Regulatory authorities working on strategies to reduce the cost of
process validation and incorporate validation consideration
during product design and development.
 New technologies under development for 100% analysis of drug
products and other innovations in pharmaceutical industry may
also have a significant effect on Validation & basic regulatory
authority's acceptance.
 The future of process validation is also of great interest, especially
with the worldwide expansion of pharmaceutical manufacturing &
for harmonizing in international standards and requirements.
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35. REFERENCES
 Pharmaceutical Process Validation by R. Berry & Robert
A. Nash.
 P. P. Sharma, Validation in Pharmaceutical Industry,
Vandana Publication Pvt. Ltd. Dehli.
 www.fda.gov/cder/guidance/pv.htm (US FDA).
 http://www.fda.gov/iceci/enforcementactions/warning
letters/2013
 www.emea.eu.int/ (EU Audit Agency).
 http://www.validation-online.net/
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